Abstract
BackgroundSenescence of the neurons is believed to be a focal factor in the development of age-related neurodegenerative diseases such as Alzheimer’s disease. Diminutions in the levels of nerve growth factor (NGF) lead to major declines in brain cell performance. Functional foods, believed to mitigate this deficiency, will be reaching a plateau in the near future market of alternative and preventive medicine. In the search for neuroactive compounds that mimic the NGF activity for the prevention of neurodegenerative diseases, the potential medicinal values of culinary and medicinal mushrooms attract intense interest.MethodsCytotoxic effects of aqueous extracts of three medicinal mushrooms basidiocarps, Ganoderma lucidum, Ganoderma neo-japonicum and Grifola frondosa towards rat pheochromocytoma (PC-12) cells were determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The potentiation of neuritogenic activity was assessed by neurite outgrowth stimulation assay. Involvement of cellular signaling pathways, mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK1/2) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) in mushrooms-stimulated neuritogenesis were examined by using specific pharmacological inhibitors. Alteration of neuronal morphology by inhibitors was visualized by immunofluorescence staining of the neurofilament.ResultsAll the aqueous extracts tested caused a marked stimulation of neuritogenesis with no detectable cytotoxic effects towards PC-12 cells. The aqueous extract of G. neo-japonicum triggered maximal stimulation of neurite outgrowth at a lower concentration (50 μg/ml) with 14.22 ± 0.43% of neurite-bearing cells, compared to G. lucidum and G. frondosa that act at a higher concentration (75 μg/ml), with 12.61 ± 0.11% and 12.07 ± 0.46% of neurite-bearing cells, respectively. The activation of MEK/ERK1/2 and PI3K/Akt signaling pathways were necessary for the NGF and aqueous extracts to promote neuritogenesis.ConclusionsGanoderma lucidum, G. neo-japonicum and G. frondosa may contain NGF-like bioactive compound(s) for maintaining and regenerating the neuronal communications network. The present study reports the first evidence of the neuritogenic effects of aqueous extracts of basidiocarps of G. neo-japonicum in-vitro and showed the involvement of MEK/ERK1/2 and P13K/Akt signaling pathways for neuritogenesis in PC-12 cells.
Highlights
Senescence of the neurons is believed to be a focal factor in the development of age-related neurodegenerative diseases such as Alzheimer’s disease
Kaighn’s Modification of Ham’s F-12 Medium (F-12 K medium), nerve growth factor (NGF)-7S from murine submaxillary gland, 3(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), phosphate buffered saline (PBS), dimethyl sulfoxide (DMSO), Mitogen-activated protein kinase kinase (MEK) inhibitor (U0126, PD98059), PI3K inhibitor (LY294002), anti-neurofilament 200 (NF200) antibody produced in rabbit and Anti-Rabbit IgGFluorescein isothiocyanate (FITC) antibody produced in sheep were obtained from Sigma Co
The inhibitors blocked the neuritogenic activity of aqueous extracts and NGF and caused shrunken and rounded cell bodies without noticeable neurite extension. These results suggest that the activation of MEK/ERK1/2 and PI3K/Protein kinase B (Akt) signaling pathways are needed for the NGF and aqueous extracts in promoting neuritogenesis
Summary
Senescence of the neurons is believed to be a focal factor in the development of age-related neurodegenerative diseases such as Alzheimer’s disease. In the search for neuroactive compounds that mimic the NGF activity for the prevention of neurodegenerative diseases, the potential medicinal values of culinary and medicinal mushrooms attract intense interest. Dementia is a brain function syndrome characterized by a cluster of symptoms and signs manifested by difficulties in memory, disturbances in language, psychological and psychiatric changes, and impairments in activities of daily living. Alzheimer's disease is one form of dementia that gradually gets worse over time. It affects memory, thinking, and behaviour [2]. Neuritogenic activity is one of the focuses of the study on the preventive and therapeutic effects of neurodegenerative diseases. Recent reports showed that many extracts or compounds from natural sources possessed significant neuritogenic activity in vitro and in vivo, included hericenones and erinacines from Hericium erinaceus (lion’s mane mushroom) [4] and curcumin from Curcuma longa [5]
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